Di Carlo E, Modesti A, Coletti A, Colombo M P, Giovarelli M, Forni G, Diodoro M G, Musiani P
Dipartimento di Oncologia e Neuroscienze, Università G. D'annunzio, Chieti, Italy.
J Pathol. 1998 Dec;186(4):390-7. doi: 10.1002/(SICI)1096-9896(199812)186:4<390::AID-PATH194>3.0.CO;2-Z.
Injection of interleukin-4 (IL4) gene-transduced tumour cells into syngeneic immunocompetent mice resulted in tumour rejection in which a key role for eosinophils was suggested. To evaluate whether IL5 inhibits tumour growth by selectively inducing eosinophil recruitment and activation, a poorly differentiated mammary adenocarcinoma cell line (TSA) was transfected with the IL5 gene and the cells secreting IL5 (TSA-IL5) were injected subcutaneously (s.c.) in syngeneic mice. The oncogenicity of TSA-IL5 was compared with that exhibited by TSA cells transfected with the IL4 gene (TSA-IL4) and with the neomycin resistance gene only (TSA-neo). At progressive times after subcutaneous challenge, tumour growth areas were studied histologically, ultrastructurally, and immunohistochemically to identify the reactive cells, visualize tumour vessels, and detect the cytokines and chemokines involved in the anti-tumour reaction. Both the morphological and the functional data showed that TSA-IL5, despite the large eosinophil infiltrate, grew progressively like TSA-neo, suggesting that eosinophils per se do not play a crucial role in TSA tumour rejection. Furthermore, our data indicate that the rejection of TSA-IL4 depends on the IL4-induced expression of VCAM-1 and MCP-1 by endothelial cells. MCP-1 together with VCAM-1 results in recruitment and activation of basophils, mast cells, and macrophages, and hence a pro-inflammatory cytokine cascade that initially favours the influx and activation of neutrophils and finally tumour rejection. In this context, the rejection of TSA-IL4 seems to involve a variety of reactive cells and rests on a continuous cross-talk between basophils, mast cells, macrophages, CD8-positive lymphocytes, and granulocyte subsets, mostly neutrophils.
将白细胞介素-4（IL4）基因转导的肿瘤细胞注射到同基因免疫活性小鼠体内会导致肿瘤排斥反应，提示嗜酸性粒细胞在其中起关键作用。为了评估IL5是否通过选择性诱导嗜酸性粒细胞募集和激活来抑制肿瘤生长，将低分化乳腺腺癌细胞系（TSA）转染IL5基因，并将分泌IL5的细胞（TSA-IL5）皮下注射到同基因小鼠体内。将TSA-IL5的致癌性与转染IL4基因的TSA细胞（TSA-IL4）以及仅转染新霉素抗性基因的细胞（TSA-neo）的致癌性进行比较。在皮下攻击后的不同时间，对肿瘤生长区域进行组织学、超微结构和免疫组织化学研究，以识别反应性细胞、观察肿瘤血管并检测参与抗肿瘤反应的细胞因子和趋化因子。形态学和功能数据均显示，尽管TSA-IL5有大量嗜酸性粒细胞浸润，但仍像TSA-neo一样逐渐生长，这表明嗜酸性粒细胞本身在TSA肿瘤排斥中并不起关键作用。此外，我们的数据表明，TSA-IL4的排斥取决于IL4诱导内皮细胞表达VCAM-1和MCP-1。MCP-1与VCAM-1共同导致嗜碱性粒细胞、肥大细胞和巨噬细胞的募集和激活，从而引发促炎细胞因子级联反应，最初有利于中性粒细胞的流入和激活，最终导致肿瘤排斥。在这种情况下，TSA-IL4的排斥似乎涉及多种反应性细胞，并且依赖于嗜碱性粒细胞、肥大细胞、巨噬细胞、CD8阳性淋巴细胞和粒细胞亚群（主要是中性粒细胞）之间的持续相互作用。
